This pulmonary vascular endothelium governs transfer of solutes between blood and tissues, and maintains a nonthrombogenic surface for circulating blood. In addition, it can control access of particular vasoactive materials to the systemic circulation by uptake and metabolism of these materials during their circulation through the lung. Our studies are focused upon the mechanisms of uptake and binding of potentially edematogenic drugs, toxins and chemicals in the rabbit lung. The specific questions to be addressed are: how do these agents in circulation injur pulmonary endothelium or change its transport properties? Is the uptake of an edematogenic agent related to its damaging effect on the pulmonary endothelium? Can either the uptake of a potentially edematogenic agent, or its effect on transport, be affected by conditions such as pH, perfusion pressure, pO2, or the presence of sulfhydryl-containing compounds? These studies are executed with two in vitro preparations, the isolated perfused rabbit lung, and pulmonary endothelial cells in culture. The isolated perfused lung provides a means to study the influence of particular agents on endothelium in situ and to measure the formation of edema, as indicated by an increase in the water content of the lungs. In addition, labeled compounds can be localized within the lung tissues using techniques of autoradiography and electron microscopy. The pulmonary endothelial cells in culture enable us to examine one particular type of cell for specific cell functions, and to determine how these are affected by edematogenic agents. The chemical agents of particular interest to us include the narcotic analgesics, salicylates, and the thiourea compounds.